Rotenone Group Research Articles

Gender differences of oxidative stress reactions in ventral mesencephalic dopamine neurons

Objective To investigate the gender differences of oxidative stress reactions in ventral mesencephalic(VM) dopamine neurons.Methods VM dopamine neurons of male and female Balb/c fetal mice were cultured,and were divided into control group(without treatment),rotenone group(treated with 25 nmol/L rotenone for 8 h) and estrogen+rotenone group(treated with 1×10-7 mol/L 17 β-estradiol for 1 h and 25 nmol/L rotenone for 8 h).Immunohistochemistry was employed to observe the neuron injury of mice of different genders,MTT assay was adopted to measure the cell viability,and Western blotting was used to detect the expression of tyrosine hydroxylase(TH) protein in cells of mice of different genders.Results Immunohistochemistry revealed that cell injury of male mice was more severe than that of female mice,and cells of male mice with positive TH were more significant than those of female mice with positive TH in rotenone group.MTT assay indicated that there were significant differences in cell viability between male mice(66%) and female mice(75%) in rotenone group(P0.05),and cell viability of male mice(81%) and female mice(86%) in estrogen+rotenone group was significantly higher than that of mice of corresponding genders in rotenone group(P0.05).Western blotting demonstrated that the expression of TH protein in cells of male mice was significantly lower than that in cells of female mice in rotenone group(P0.05),and the expression of TH protein in estrogen+rotenone group was significantly higher than that of corresponding genders in rotenone group(P0.05).Conclusion There exist gender differences of oxidative stress reactions in VM dopamine neurons.Male is more vulnerable than female in respond to rotenone,and estrogen has protective effects on both male and female neurons.

The rotenone-induced rat model of Parkinson's disease: Behavioral and electrophysiological findings

Exposure to rotenone leads to parkinsonian features, such as loss of dopaminergic neurons in the substantia nigra and motor impairment, however, the validity of this model has recently been questioned. In rodent and monkey models of Parkinson's disease (PD) abnormal neuronal activity in the basal ganglia motor loop has been described, with hyperactivity of the subthalamic nucleus (STN) similar to that found in PD. The present study aims at providing new and more specific evidence for the validity of the rotenone rat model of PD by examining whether neuronal activity in the STN is altered.Male Sprague Dawley rats were treated with rotenone injections (2.5mg/kg bodyweight intraperitoneally) for 60 days. Behavioral analysis showed an impairment in the rotarod and hanging wire test in the rotenone group (p<0.05), accompanied by a decline in tyrosine hydroxylase immunoreactive neurons in the nigro-striatal region (p<0.001). Thereafter, single unit (SU) activities and local field potentials were recorded in the STN in urethane anesthetized rats. The SU analysis revealed a higher neuronal discharge rate (p<0.001), more bursts per minute (p=0.006) and a higher oscillatory activity (p=0.008) in the STN of rotenone treated rats. Spectral analysis showed an increase of relative beta power in the STN as well as in the motor cortex.We found electrophysiological key features of PD pathology and pathophysiology in the STN of rotenone treated rats. Therefore, the rotenone-induced rat model of PD deserves further attention since it covers more aspects than dopamine depletion and implies the reproducibility of PD specific features.

Characterization of motor, depressive-like and neurochemical alterations induced by a short-term rotenone administration

BackgroundRotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy of rotenone as an animal model of Parkinson’s disease (PD). In this study, we investigated the motor and depressive-like behaviors associated to neurochemical alterations induced by a novel protocol of rotenone administration. MethodsIn the first experiment, we adopted the paw test to characterize an effective dose of rotenone able to promote nigrostriatal toxicity. In the second experiment, control and rotenone 2.5mg/kg groups were injected (ip) for 10 consecutive days. ResultsThis test indicated that intraperitonial (ip) rotenone at 2.5 and 5.0mg/kg promoted a significant neurotoxicity to striatum and nucleus accumbens. However, only 2.5mg/kg of rotenone was associated to a negligible mortality rate. Open-field tests were conducted on 1, 7, 14 and 21 day after the last day of treatment and showed an important locomotor impairment, confined to 1 and 7 day. Besides, rotenone affected dopamine levels and increased its turnover in the striatum. Modified forced swim test (performed on 22 day) and sucrose preference test (performed on 14 and 21 day) demonstrated that rotenone produced impairments in the swimming and immobility. In parallel, increments in the serotonin and noradrenaline turnovers were observed in the striatum and hippocampus of the rotenone group. ConclusionsThese data suggest important participations of serotonin and noradrenaline in depressive-like behaviors induced by rotenone. Thus, it is proposed that the current rotenone protocol provides an improvement regarding the existing rotenone models of PD.

Selective protection of nigral dopaminergic neurons by echinacoside in a rat model of Parkinson disease induced by rotenone

To observe the protective effects of echinacoside on rotenone-induced damages in rats. Healthy male Sprague-Dawley rats, weighing from 200 to 220 g, were randomly divided into five groups with 20 rats in each group: control group, rotenone group and echinacoside groups of low, medium and high doses (20, 40 and 80 mg/(kg·d)). Rats in the rotenone group were injected intraperitoneally for four weeks with rotenone (2.75 mg/(kg·d)), dissolved into dimethyl sulfoxide; rats in the control group were injected intraperitoneally with dimethyl sulfoxide daily, and rats in the echinacoside groups received daily intraperitoneal injection of rotenone along with echinacoside gastric perfusion for four weeks. Modified neurological severity score was used to evaluate neurobehavior of the animals; dopaminergic neurons in substantia nigra were observed by immunochemical method and dopamine concentration in striatum was determined by a fluorescence spectrophotometer. Biomarkers of liver and kidney damage were also measured. In the rotenone group, the rats suffered from severe neurological disability (P<0.01), and the number of dopaminergic neurons in substantia nigra and dopamine concentration in striatum were decreased (P<0.05) compared with the normal control group; levels of the biomarkers for evaluating liver and kidney damage were increased (P<0.05). In the echinacoside groups, the neurological disability and the loss of dopaminergic neurons in substantia nigra were suppressed and dopamine concentrations in striatum were increased (P<0.05), but the liver and kidney damage was not improved (P>0.05). Rotenone causes severe damages to dopaminergic neurons, liver and kidney in rats and echinacoside selectively reverses dopaminergic neuronal injury.

Acetyl-l-carnitine and α-lipoic acid affect rotenone-induced damage in nigral dopaminergic neurons of rat brain, implication for Parkinson's disease therapy

Although the mechanisms of neurodegeneration in Parkinson's disease are not fully understood, mitochondrial dysfunction, oxidative stress and environmental toxins may be involved. The current research was directed to investigate the protective role of two bioenergetic antioxidants, acetyl-l-carnitine and α-lipoic acid, in rotenone-parkinsonian rats. Ninety six male rats were divided into five groups. Group I is the vehicle-injected group, group II is the disease control group and was injected with six doses of rotenone (1.5mg/kg/48h, s.c.). Groups III, IV and V received rotenone in addition to acetyl-l-carnitine (100mg/kg/day, p.o.), α-lipoic acid (50mg/kg/day, p.o.) or their combination, respectively. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field and square bridge tests. In addition, ATP level was decreased whereas lipid peroxides and protein carbonyls increased in the striata of rotenone-treated rats as compared to vehicle-treated rats. Treatment with acetyl-l-carnitine or α-lipoic acid improved the motor performance and reduced the level of lipid peroxides in rat brains as compared to rotenone group. Further, ATP production was enhanced along with acetyl-l-carnitine treatments (p≤0.05). Taken together, our study reinforces the view that acetyl-l-carnitine and α-lipoic acid are promising candidates for neuroprotection in Parkinson's disease.

Relative contributions of mitochondria and NADPH oxidase to deoxycorticosterone acetate-salt hypertension in mice

We assessed the relative contribution of the mitochondrial respiratory chain and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase to deoxycorticosterone acetate (DOCA)-salt hypertension in mice. The daily mean arterial pressure was monitored by radiotelemetry in DOCA-salt-treated mice given vehicle or the mitochondrial respiratory chain complex I inhibitor rotenone. This treatment produced remarkable attenuation of DOCA-salt hypertension. Similar results were obtained with other inhibitors of mitochondrial function, including 5-hydroxydecanoate (specific for mitochondrial potassium-ATP channels), benzylguanidine (complexes I and III), and the cell-permeable manganese tetrakis (4-benzoic acid) porphyrin (a mimic of mitochondrial superoxide dismutase). In parallel with the blood pressure-lowering effect of rotenone, the DOCA-salt-induced increases in urinary 8-isoprostane excretion and in reactive oxygen species production of isolated kidney mitochondria were both significantly attenuated. Conversely, the DOCA-salt-induced reduction of urinary nitrate/nitrite excretion was significantly elevated. Following DOCA-salt treatment, mice deficient in NADPH oxidase subunits gp91(phox) or p47(phox) exhibited a partial attenuation of the hypertensive response at early but not later time points. Thus, the mitochondrial respiratory chain is a major source of oxidative stress in DOCA-salt hypertension, whereas NADPH oxidase may have a relatively minor role during the early stage of hypertension.

Protective effects of caffeic acid phenethyl ester on rotenone-induced myocardial oxidative injury

Rotenone, an insecticide, causes toxicity through inhibition of mitochondrial electron transport chain at complex I and oxidative injury to the tissues. The aim of the present study was to determine in vivo effects of rotenone on myocardium and cardio-protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, against rotenone toxicity in rats. The rats were divided into three groups: untreated control, rotenone (2.5 mg/kg/day for 60 days, i.p.) and rotenone + CAPE groups. CAPE was administrated i.p. 10 μmol/kg/day for 62 days started two days before first dose rotenone injection. The malondialdehyde, nitric oxide levels and xanthine oxidase activity of rotenone group was significantly higher than control and rotenone + CAPE groups ( p < 0.05). However, catalase activity in the rotenone group was decreased in comparison with the other groups ( p < 0.05). The superoxide dismutase activity of rotenone group was insignificantly decreased compared to the others. In conclusion, rotenone caused lipid peroxidation in myocardial tissue and CAPE treatment prevented this rotenone-induced lipid peroxidation in rats. CAPE might be a cardio-protective agent against myocardial toxicities.

1005 Inflammation-related genes affect age at onset of Parkinson's disease

Aim: To investigate the protective effect of Pituitary adenylate cyclase activating polypeptide27 (PACAP27) on rotenone-induced cytotoxicity in PC12 cells. MeillOdS: PC12 cells differentiated by nerve growth factor as dopaminergic neurons were treated by different concentrations of rotenone; Cell viability was assessed with MTT and cell apoptosis was detected by Annexin-V staining and flow cytometry; mRNA of PACI receptor was analyzed by RT-PCR. Results: The expression of the mRNA for PACAP receptor (dominant PAC1 receptor) in PC12 cells was demonstrated by RT-PCR; The cell viability was declining with the concentration of rotenone increasing and this neurotoxicity demonstrated dose-dependent manners; PAC.AP27 (10-7--10 -~a mol.L -1) showed significant neuroprotective effects against rotenone-indued toxicity; A decrease in the occurrence of late apoptotic features was found by double staining with Annexin-V and propidium iodide (PI) in rotenone+PACAP27 groups, compared with rotenone group; Flow cytometry results showed PACAP27 could improve the cell viability by decreasing the numbers of apoptotic cells, but this effects can be reversed by PAC.APs 27, a kind of PACAP receptor antagonist. Conclusion: These results suggest that PACAP may exert a protective effect against rotenone-induced neurotoxicity by PAC1 receptor in PC12 cells.

Protective effects of erdosteine on rotenone-induced oxidant injury in liver tissue

Rotenone, an insecticide of botanical origin, causes toxicity through inhibition of complex I of the respiratory chain in mitochondria. This study was undertaken to determine whether rotenone-induced liver oxidant injury is prevented by erdosteine, a mucolytic agent showing antioxidant properties. There were four groups of Male Wistar Albino rats: group one was untreated as control; the other groups were treated with erdosteine (50 mg/kg per day, orally), rotenone (2.5 mg/mL once and 1 mL/kg per day for 60 days, i.p.) or rotenone plus erdosteine, respectively. Rotenone treatment without erdosteine increased xanthine oxidase (XO) enzyme activity and also increased lipid peroxidation in liver tissue (P < 0.05). The rats treated with rotenone plus erdosteine produced a significant decrease in lipid peroxidation and XO activities in comparison with rotenone group (P < 0.05). Erdosteine treatment with rotenone led to an increase in catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the rotenone group (P < 0.05). There was no significant difference in nitric oxide (NO) level between groups. There were negative correlations between CAT activity and malondialdehyde (MDA) level (r = -0.934, P < 0.05) with between CAT and SOD activities (r = -0.714, P < 0.05), and a positive correlation between SOD activity and MDA level (r = 0.828, P < 0.05) in rotenone group. In the rotenone plus erdosteine group, there was a negative correlation between XO activity and NO level in liver tissue (r = -0.833, P < 0.05). In the light of these findings, erdosteine may be a protective agent for rotenone-induced liver oxidative injury in rats.

THE LACK OF SCION EFFECT ON ROOT QUALITY OF DERRIS ELLIPTICA

In rotenone-bearing crops, such as Derris elliptica (Wall.) Benth., in which the root is valued for insecticidal purposes, the yield of root as well as the rotenone content is important. Obviously yield could not be sacrificed to obtain high rotenone percentage, nor could high yield compensate for low rotenone content. A maximum yield of root of uniformly high rotenone content may be considered as a goal. Of the several types of D. elliptica available at this station, one, the St. Croix variety, is characterized by a high yield of root markedly low in rotenone. Another, Changi No. 3, is characterized by a lower yield of root which is relatively high in rotenone. A third variety, the Sarawak Creeping, occupies an intermediate position with regard to rotenone content. The extent to which grafting may modify the yield and rotenone content in Derris roots has never been investigated. The possibility of increasing the rotenone content of the more vigorous St. Croix roots by grafting on scions of the Changi No. 3 seemed promising. Likewise, St. Croix tops on Changi No. 3 roots might increase the yield of roots of the latter. An experiment testing these premises is here reported, the results of which, although negative with regard to the anticipated scion effect, are of interest. A hypothesis under test in this experiment concerned the possibility of the leafy part of the plant supplying some factor, perhaps an intermediate compound, similar to but simpler than rotenone, which was necessary for the completion of the synthesis of rotenone in the roots. This was suggested by the fact that compounds of the rotenone group are chemically related to compounds of the flavone group, of which at least two occur in the leaves of derris.2 Rotenone itself (I) can be considered as an isoflavanone nucleus (II) in which a methoxyl group on 6' is condensed with a hydroxyl group on 2 to result in a bridge. On 7 and 8 there is a pentose residue and on 3' and 4 methoxyl groups. That compounds related to rotenone exist in the root in glycosidic combination (probably acylated) is indicated by the fact that derris resin must be hydrolyzed by mild alkali treatment before crystalline deguelin can be isolated. Methods

Occurrence of Rotenone in Tephrosia macropoda Harv

IN an investigation of the contact insecticidal properties of a number of tropical plants, Tattersfield and Gimingham4 found that the roots of a specimen of T. macropoda Harv. from Natal possessed a definite toxicity to Aphis rumicis. Other members of the genus known to possess insecticidal action have been examined chemically1,2,3,5,6, and have been found to contain members of the rotenone group of fish-poisoning compounds. We have recently been able to carry out preliminary tests upon a specimen of T. macropoda kindly sent to us by the Natal Herbarium, Department of Agriculture, Durban. The material was collected by Mr. Moses, agronomist attached to the African Explosives and Industries, Ltd.